Cardiopulmonary Responses to Exercise and Its Utility in Patients With Aortic Stenosis Abhijeet Dhoble, MD, MPH a,b, *, Maurice Enriquez-Sarano, MD b , Stephen L. Kopecky, MD b , Sahar S. Abdelmoneim, MD, MS b,c , Paulina Cruz, MD b , Randal J. Thomas, MD, MS b , and Thomas G. Allison, PhD, MPH b Utility of cardiopulmonary exercise test is unknown in patients with aortic stenosis. In this retrospective study, we examined the maximal indexes of cardiopulmonary testing at peak exercise in 155 consecutive patients with aortic valve area of £1.5 cm 2 who were referred for this test. The patients were passively followed up to assess their effect on the primary end point of all-cause mortality. We found that the absolute peak oxygen consumption (VO 2 ) was significantly reduced in these patients, with age and genderepredicted peak VO 2 of 80 – 23%. Peak VO 2 was markedly reduced (<80% of predicted) in 54% of patients. During a follow-up of 5 – 4 years, a total of 41 patients died, and 72 underwent aortic valve replacement. Survival was significantly better in patients with higher absolute peak VO 2 (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.80 to 0.93, p <0.001) and higher oxygen pulse (HR 0.80, 95% CI 0.74 to 0.9, p <0.001). In 83 patients who did not undergo valve replacement, higher peak VO 2 and oxygen pulse were associated with better survival (HR 0.83, 95% CI 0.71 to 0.97, p [ 0.024 and HR 0.80, 95% CI 0.66 to 0.96, p [ 0.02, respectively). In conclusion, the peak VO 2 is significantly reduced in patients with aortic stenosis. Higher peak VO 2 is independently associated with better survival in these patients irrespective of whether they undergo valve replacement. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:1711e1716) Symptom-limited cardiopulmonary exercise testing (CPX) assists in differentiation of cardiac limitation from pulmonary or other limitation as a cause of exercise-induced symptoms. 1e3 CPX has a definite role in risk stratification in patients with coronary artery disease, 4 heart failure, 5,6 and hypertrophic cardiomyopathy 7 but has been underused for risk assessment in patients with aortic stenosis (AS). Current guidelines recommend valve replacement in symptomatic patients with severe AS. 8 However, some patients who claim to be asymptomatic may have limited their physical activity to avoid symptoms. Additionally, many patients, especially elderly, have mild or equivocal symptoms that are difficult to distinguish from effects of aging, deconditioning, or obesity. CPX with determination of gas exchange pro- vides quantitative, objective, and noninvasive evaluation of cardiopulmonary fitness and estimate of cardiac output. 1,3,9 To our knowledge, there are very few studies that have systematically examined the clinical and prognostic utility of CPX in patients with AS. In the present study, we examined the indexes of CPX at peak exercise and assessed their association with mortality. Methods From 1994 to 2009, a total of 375 patients with the diagnosis of AS were referred for CPX to our Cardiopul- monary Exercise Testing Laboratory at Mayo Clinic, Rochester. We excluded patients with previous aortic valve (AV) surgery, moderate to severe aortic regurgitation, sig- nificant multivalvular involvement, AV area of >1.5 cm 2 on echocardiographic assessment, systolic heart failure, and the patients who gave submaximal efforts during exercise indicated by respiratory exchange ratio of 1. Five addi- tional patients were excluded because they denied access to their medical records. Thus, the final study population (Figure 1) consisted of 155 patients with moderate to severe AS according to the current classification scheme. 8 The study was approved by the Mayo Clinic Institutional Review Board. Baseline characteristics of the population were recorded on the day of CPX. This included their heart rate at rest, blood pressure, body mass index, electrocardiogram, his- tory of previous cardiac surgery, medication use, and co- morbidities including presence of coronary artery disease, hypertension, diabetes, and dyslipidemia. A physician (PC) performed the detailed chart review of the subjects for symptoms. To validate this abstracting procedure, a second physician (AD) reabstracted this information on a random sample of 15 patients (w10%). The interrater agreement on the abstracted data was 100%. Each patient underwent a symptom-limited maximal CPX with respiratory gas exchange analysis using an accelerated Naughton protocol as previously described (2-minute workloads, 2 METs/min increments in work). 10,11 Patients a The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, Cali- fornia; b Cardiopulmonary Exercise Testing Laboratory, Division of Car- diovascular Diseases, Mayo Clinic, Rochester, Minnesota; and c Division of Cardiovascular Medicine, Assiut University, Assiut, Egypt. Manuscript received November 23, 2013; revised manuscript received and accepted February 12, 2014. See page 1715 for disclosure information. *Corresponding author: Tel: 507-774-9601; fax: 507-266-0228. E-mail address: abhijeetdhoble@gmail.com (A. Dhoble). 0002-9149/14/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. www.ajconline.org http://dx.doi.org/10.1016/j.amjcard.2014.02.027